本研究将聚焦于恶性肿瘤微环境演进的可视化，解析肿瘤肝转移过程中肿瘤细胞与肿瘤微环境之间的相互作用、介导该相互作用的关键分子及其调控机理。我们已利用功能基因组学的策略即CRISPR-Cas9全基因组敲除文库筛选出调节肿瘤肝转移的关键分子-Ermap。进一步研究发现肿瘤细胞膜表达的Ermap可被肝脏Kupffer细胞表面的Galectin-9/Dectin-2识别，从而促进Kupffer细胞对肿瘤细胞的吞噬，抑制肿瘤肝转移。因此，本项目拟进一步探讨肿瘤肝转移过程之肿瘤细胞于肝脏定植这一关键限速步骤中肿瘤细胞与Kupffer细胞的相互作用，Ermap/Galectin-9/Dectin-2介导该相互作用的详细分子机理，及进而对肿瘤微环境的调控作用和机制。并且以该关键分子事件为靶点，开发靶向抗体-荷钆纳米探针等实现对肿瘤肝转移的可视化预警、诊断与靶向治疗。

In this study, we will focus on the visualization of tumor microenvironment progressions and investigate the interaction between cancer cells and tumor microenvironment during tumor liver metastasis, the molecules mediating the interaction, and the functional visualization of the molecules. We have identified Ermap as the critical molecule regulating tumor liver metastasis via functional genomic strategy and CRISPR-Cas9 full-genome knocking out library. Further studies found that Ermap expressed on the membranes of cancer cells could be recognized by Galectin-9/Dectin-2 expressed on the membranes of Kupffer cells, which further promoting the phagocytosis of cancer cells by Kupffer cells and inhibiting liver metastasis. Thus, in this study, we will further investigate the interaction between cancer cells and Kupffer cells during liver colonization, which is the critical rate-limiting step of liver metastasis. We will also elucidate the detailed molecular mechanisms exerting by Ermap/Galectin-9/Dectin-2, and their further modulatory roles on tumor microenvironment. Using these critical molecules as targets, we will develop antibody-gadolinium loaded nanoprobe to predict, diagnose, and treat liver metastasis.